Electrophysiological investigation of IDPN neuropathy--initial studies

Abstract

beta,beta'-iminodipropionitrile (IDPN) causes giant axon swellings in proximal internodes of spinal motor axons and in stem processes of dorsal root ganglia neurons. The electrophysiological consequences of the swellings were investigated in cats given IDPN (50 mg/kg i.p.) weekly for 0 (control), 1 (7 days), 2 (14 days), or 5 (35 days) weeks; some additional animals were studied 15 (50 days) or 65 (100 days) days following the fifth injection. Extracellular recordings of the spinal monosynaptic reflex revealed amplitudes of efferent responses to be equally reduced at 35, 50 and 100 days. Single stimulation of dorsal roots, or soleus or medial gastrocnemius afferents often evoked doublet efferent responses which arose intraspinally. Similar repetitive responses were observed in dorsal root (afferent) input upon single stimulation of peripheral nerves. Latencies to monosynaptic responses became progressively prolonged over 100 days; spinal cord contribution to the increased latencies was maximal by 35 days. Conduction velocities in single soleus and medial gastrocnemius axons declined to 70 and 64% of normal by 50 days and to 56 and 50% of normal by 100 days respectively. Maximal recurrent inhibition was reduced 42-49% by 35 days and quantitatively similar at 50 and 100 days. Intracellular recordings from spinal motoneurons revealed that, at 35 days, action potentials could be elicited by orthodromic but not by antidromic stimulation in 14% of cells tested. This was taken as evidence of block of impulse conduction by the intervening axonal swelling upon antidromic stimulation. The possibility of abnormal electrical interactions between swollen and demyelinated intraparenchymal axons was tested by determining the number of ventral root fibers via which antidromic stimulation would elicit an action potential in the same motoneuron perikaryon. Electrical crosstalk, never seen in normal animals, varied in incidence during the evolution of the neuropathy (7-35 days), reaching a maximum of 30% at 14 days. Many motoneuron action potentials were remarkably similar to those observed in chromatolytic motoneurons, exhibiting, among other features, decreased SD thresholds and IS conduction times, reduced amplitudes and durations of afterhyperpolarization, delayed depolarizations and an enhanced propensity to fire repetitively upon single stimulation. There was no morphological evidence of chromatolysis in the motoneurons. The concept of "functional axotomy" is introduced to accommodate these findings and discussed in terms of altered dendritic excitability. Not all motoneuron types are equally compromised in the neuropathy.(ABSTRACT TRUNCATED AT 400 WORDS)